1. Field of the Invention
The present invention generally concerns shakers, and laboratory shakers.
The present invention particularly concerns a laboratory shaker that is high performance in each of (i) shaking rate, (ii) shaking amplitude, (iii) load capacity, (iv) versatility in the amount, weight, numbers and sizes of containers and samples that are shaken, (v) overall compactness, (vi) durability, (vii) quietness and lack of vibration in operation, and (vii) programmability.
2. Description of the Prior Art
2.1 General Description of the State of the Laboratory Shaker Art
The cost of laboratory space, and efficiencies of human access and use, dictate that laboratory equipments, including shakers, should be compact and powerful, with a large load capacity, wherever and whenever possible. Moreover, shakers, in particular (along with stirrers, which have an overlapping function and purpose), may be called upon to handle a broad range of analysis protocols, and of biological samples. For example, as well as performing common shaking at, most typically, several tens of hundreds of cycles per minute, new and increasingly popular laboratory protocols call for biological materials to be mixed with ceramic beads and then shaken, preferably at many thousands of oscillations per minute, until cellular and sub-cellular structures are completely obliterated, loosing the biological constituent components, including genetic components, of the materials into a sort of biological broth, or stew.
Present-day (circa 2000) laboratory shakers that are capable of shaking samples, such as biological samples, at high, multi-thousand cycle per minute (cpm) rates typically have low load capacities, on the order of less than one ounce (1 oz.) Conversely, those shakers that have broad and ample load ranges (1-8 oz.) are often capable of performing shaking at but low speeds, a only some few tens or hundreds of cycles per minute (cpm). There is, however, no systemic difference in the amount of material to be shaken between the high-speed and low-speed shaking protocols: it is quite common to wish to shake many ounces at high speed.
The reason that present laboratory shakers are limited in shaking at high speeds such loads as are common is not the required energy for shaking. Many shakers have large fractional horsepower motors that should be able to develop the forces to shake and propel samples weighing several ounces at high oscillatory speeds. However, the bearings of most motors will not directly withstand the inertial forces of shaking, which requires mechanical isolation of the shaking motion from the motor drive. This mechanical isolation, and the shaking itself, produces prodigious vibration and noise. Unless the shakers are strongly anchored to extremely large and massive structures, most preferably to the steel frames of steel-frame buildings, they tend to produce abominable noise and vibration. If and when the shakers are xe2x80x9ctunedxe2x80x9d for reduction of certain harmonics then they tend to have a limited operational ranges in both (i) permissible load, and (ii) shaking speed, and become all but unusable outside these ranges. And, when the shakers are anchored firmly to earth then huge forces are applied to the bearings of the shaker, making that the shaker must itself be massive to withstand the forces that it produces.
Accordingly, it would be useful if some approach existed to xe2x80x9cfinessexe2x80x9d the operational and structural problems of the traditional laboratory shaker, and if it were somehow to be possible build a compact and economical broad-range high-performance shaker in which the considerable forces of shaking did not translate into large mass for the shaker, vibration and noise.
In another area, the slower-paced era wherein laboratory samples that required shaking could be manually transferred into containers, mostly glassware and most commonly test tubes, that could be physically accommodated by the shaker is now past. Most modern shakers make some effort to accommodate such a range of sample containers as the manufacture of the shaker envisions will be in use by purchasers of the shaker. However, no manufacturer, or purchaser, can foresee every eventuality, and the sample containers that are, or become, required by certain laboratory equipments may turn out to be unsuitable for use with the shakers of the same laboratory, or of other laboratories. It would thus be useful if some sort of shaking system could be derived where the mechanized operation of the shaker was to some degree separated from the packaging of the samples shaken, perhaps by providing some sort of jig by which various sample packages, and new-type sample packages not even in existence when the shaker was built, could be conveniently adopted to the shaker.
Of course, a jig presents its own problems. Its mass must be added to that of the samples, and sample containers, as the load experienced by the shaker. Accordingly, the jig should be lightweight. However, if must also be strong to withstand the inertial forces of shaking. It would be useful if the manner of attachment of the jig to the shaker could somehow support of such a xe2x80x9cstrong but lightxe2x80x9d jig construction.
A great proliferation of different jigs also presents its own cost, management and usage problems. When every different sample container requires its own special jig then the procurement cost, and cost of use, of (i) adapting the sample containers to the shaker through one or more jigs may rival the cost of (ii) directly adapting the sample containers to the shaker by transferring samples in incompatible containers into compatible containers. Accordingly, it would be useful if some limited number of jigs, or types of jigs, as are envisioned for use with a standard shaker could show both (i) widespread compatibility with existing laboratory sample containers and (ii) good potential for successful adaption to types of sample containers that may not even yet exist.
Finally, the shaker is currently one of the xe2x80x9cdumbestxe2x80x9d instruments in the laboratory. It is untenable that a human must set and re-set multiple speed and duration parameters for common shaking tasks that are regularly repetitively performed. The task is time-consuming and onerous, especially when a shaking protocol is bifurcated, with, most typically, so many minutes at one speed and then so many minutes at another speed, making that a human must stand by the shaker. If a human is charged to often set and re-set parameters then errors may occur. It would be useful if the shaker could be programmed but once for certain standard shaking protocols in use in the laboratory, and could thereafter re-create these protocols at the xe2x80x9ctouch of a buttonxe2x80x9d.
2.2 Specific Previous Laboratory Shakers and Specimen Holders of Relevance to the Present Invention
A laboratory shaker of traditional form for use in general laboratory testing and analysis is shown in U.S. Pat. No. 5,167,928 to Kelly, et. al. for a LABORATORY SHAKER APPARATUS. The apparatus comprises a base that is reciprocally movable relative to a sub-base. A frame is mounted to the base and includes spaced apart vertical supports with a horizontal support assembly rotatably mounted therebetween. A number of test vessels are mounted to the horizontal support assembly and can be rotated with the horizontal support assembly 180xc2x0 relative to the base. The vessels may be subjected to simultaneous shaking for identical periods of time. The horizontal frame assembly to which the vessels are mounted can be inverted between adjacent periods of shaking to permit selected refilling of the vessels, escape of gases therefrom and drainage of material from the vessels.
Another shaker of this formxe2x80x94this time with a more complex motionxe2x80x94is shown in U.S. Pat. No. 4,345,843 to Berglund, et. al. for an AGITATOR.
Finally, the present invention will be seen to perform shaking on test tubes that are held in racks. A test tube rack holder for supporting a test tube rack on a rotary shaker is shown in U.S. Pat. No. 4,770,381 to Gold for a TEST TUBE RACK HOLDER.
A particular commercial laboratory shaker that may usefully be compared with the shaker of the present invention is made by Savant Instruments, Inc. of Holbrook, N.Y., and sold by the assignee of the present invention, Q-Biogene of Carlsbad, Calif. The existing shaker is capable of the same high 6,000 oscillations per minute which will be seen to be the nominal maximum speed of the shaker of the present invention. However, its load capacity is only eight 2-milliliter (2 ml.) test tubes, or about {fraction (1/7)} of an ounce sample weight, at that speed. The shaker of the present invention will be seen to hold about sixteen times (xc3x9716) as much. The peak-to-peak amplitude of the Savant shaker is about 0.625 inches (⅝xe2x80x3), whereas the peak-to-peak amplitude of the shaker of the present invention will be seen to be 0.750 inches (xc2xexe2x80x3) Moreover, the shaker of the present invention will be seen to mount a plethora of different containers, and to perform its shaking function with much less vibration and noise.
2.3 Previous Laboratory Protocols Including Shaking
The shaker of the present invention will be seen to be suitable to perform virtually all presently-known, circa 2000, laboratory protocols that call for shaking. The shaker is in particular suitable to perform the protocol of U.S. Pat. No. 5,643,767 to Fischetti and Cheung for a PROCESS FOR ISOLATING CELLULAR COMPONENTS.
In the Fischetti and Cheung process a particular reagent, method and container permits the isolation of cellular components such as ribonucleic acid (RNA) from cells in a liquid solution. The container includes a cover assembly and a holder which is normally closed by the cover assembly and contains an RNA extractant solvent, micron-sized particles and at least one larger particle suitably of millimeter size. The container contains the reagent, which is an extractant solvent which contains phenol and guanidinium thiocyanate or guanidinium chloride and has a pH of about 4. The container also includes a friable sealing layer which separates the extractant solvent from the liquid medium containing the cells until the container is reciprocally shaken. The method includes the reciprocal shaking of the container, wherein the larger particle breaks the friable layer to permit mixing of the liquid medium with the extractant solvent resulting in the breaking of the cell walls by the micron-size beads and the release of the RNA.
The present invention contemplates a broad-range high-load fast-oscillating high-performance reciprocating programmable laboratory shaker directed to consistently reliably shaking usefully large amounts of samples, normally biological specimens, contained within variable numbers of diverse containers at controllably selected speeds and durations. Such shaking as may be programmably selected particularly permits, among other results, the agitation of a larger quantity of cells than heretofore at larger amplitudes than heretofore so strongly that the cell walls become broken, leaving cellular components and RNA in liberated solution, more quickly than heretofore.
The performance difference relative to previous shakers is one of kind as well as degree; comparable in nature and effect to high-speed whipping versus slow-speed stirring in a common kitchen blender. Nonetheless to its economical construction, the shaker of the present invention exhibits sufficiently high performance to reduce many slow and repetitive laboratory tasks previously involving the shaking of many small samples in small lots over half-hour, hour and longer periods into a single, quickly-performed, task of shaking all the samples together at high speed while a laboratory technician waits, most typically, only a few minutes or less.
The approach of the present invention to realizing such a high performance shaker is to counteract the inertial forces inevitably developed within the shaker, canceling wherever possible these forces with equal and opposite forces. Since the equal but opposite force cancellation occurring within the shaker is substantially independent of the (i) load and (ii) shaking speed, the shaker has (i) an unusually high load capacity, commonly ranging to sample(s) total weight(s) aggregating one pound (1 lb.) and more, and (ii) a broad operational range, typically ranging to some six thousand oscillatory cycles per minute (6,000 cpm). Such a (i) large load and (ii) high speed is unprecedented in an instrument of the modest size and cost of the preferred embodiment of a shaker in accordance with the present invention.
Additionally, the present invention contemplates versatile jigs each of which serves to efficiently adapt any number (up to a typically large maximum number) of a large number of different, and differently-sized, laboratory specimen containers to a standard shaker in accordance with the present invention. The jigs are versatile, as well as being lightweight and strong, because they use both (i) fitted inserts custom to the sample containers held and (ii) standard xe2x80x9cboxxe2x80x9d enclosures that retain the fitted inserts, and held samples, by clamping force.
Finally, the present invention contemplates a programmable shaker where a large, unambiguous and ergonomic control panel permits that a technician may enter any desired shaking protocol (in terms of standard parameters such as the times and frequencies of multiple shaking and rest periods) but once, and may thereafter invoke this pre-programmed protocol by simply touching a push button function switch.
1. Performance of a Shaker in Accordance with the Present Invention
Commensurate with its use to pulverize diverse biological samples, the laboratory shaker of the present invention exhibits high performance in several different areas. The shaking rate is controllable from, typically, 300 cycles per minute (cpm) to a very high 6000 cpm. The shaking amplitude, even at higher cpm""s, is typically at least one-half inch (xc2xdxe2x80x3), and is more typically three-quarters inch (xc2xexe2x80x3) peak-to-peak. The shaker will so perform without overheating or otherwise incurring any problems whatsoever for a minimum period of four minutes; which period suffices to pulverize all normal biological samples.
The shaker normally sets, unattached, upon a table or bench top. Even when fully loaded, the shaker imparts negliable vibration to the table or bench during operationxe2x80x94which has not always previously been the case with laboratory shakers. The airborne noise generated by the shaker is roughly equivalent to a kitchen blender, and is thus much better than average. The shaker has an indefinite operational lifetime that should extend, with periodic cleaning and lubrication, many years.
The preferred shaker mounts jigs that serve to hold various numbers of different, and differently-sized, containers of, most typically, biological samples. From one to several dozen samples that are shaken at one time may cumulate up to, most typically, some sixteen ounces (16 oz.), or one pound (1 lb.), in weight.
2. Theory of the Construction of a Shaker in Accordance with the Present Invention
The preferred embodiment of a shaker in accordance with the present invention maximizes performance by the broad strategies of (i) symmetry, and (ii) simultaneously conducting two cyclic operations oppositely at a one hundred and eighty degree (180xc2x0) phase difference between the duplicate operations. These strategy (i) is applied once (in a comprehensive manner, incorporating many separate mechanical elements), but the strategy (ii) is applied two separate and distinct times. Thus the two strategies (i), (ii) taken togetherxe2x80x94and to the same purpose of producing high performance with low vibration and noisexe2x80x94are applied three separate times, and in three separate areas.
Both the (i) symmetry, and the (ii) simultaneous conduct of two sets of identical operations each at diametrically opposite phase, imparts such xe2x80x9cforce balancexe2x80x9d to the shaker as compensates for the rapidly reciprocating motion of both (i) certain of the shaker""s parts, and (ii) the shaker""s load, and serves to greatly reduce noise and vibration.
The description of the mechanism in which these strategies are realized is as follows. In order to produce reciprocating motion of a specimen that is held within a container, the shaker of the present invention uses (i) a motor to turn (ii) a crankshaft to which is eccentrically affixed (iii) a linkage that connects to (iv) a piston attaching the container. Rotary motion induced in the crankshaft by the motor causes reciprocating linear motion in the piston affixing the specimen container, all as is substantially conventional. This mechanism, which is analogous to the like-named components of an internal combustion engine, is well-known as a basis of converting rotary motion into linearly reciprocating motion.
However, in accordance with the present invention, this classic mechanism is implemented with particular care to balance (insofar as is possible) the forces incurred during the shaking.
In accordance with a first aspect of the present inventionxe2x80x94the application of symmetryxe2x80x94the entire shaker is based on equal but opposite structures, and shows substantial mirror symmetry. In particular, a motor of the shaker has a double-ended shaft which affixes an identical crankshaft at each shaft end. The mere existence of two, as opposed to one, complimentary crankshafts serves to minimize such vibration and bearing stress in the motor as would otherwise occur from driving an eccentric body at one end only of the motor""s shaft.
A imaginary vertical plane that passes through the center of gravity of the shaker, and also of the shaker when fully loaded, passes substantially through the middle of the motor. Forces that are (i) equal but (ii) opposite at (iii) an equal moment arm of separation from this imaginary vertical planexe2x80x94and how such particularly balanced forces might come to exist will be next discussedxe2x80x94may thus be considered to mechanically couple through the vertical middle of the motor, and of the shaker apparatus. This is exactly what is desired if the apparatus is to be left-right back-fore xe2x80x9cbalancedxe2x80x9d, and without any favored distribution of weight or of force.
In accordance with a separate and severable second aspect of the present invention, and the first application of the xe2x80x9cequal but oppositexe2x80x9d principle, each crankshaft and its associated connecting linkage and piston are both statically and dynamically balanced. Static balance is achieved by adding weight to the crankshaft equally and oppositely to that structure of the crankshaft that is used to attach the connecting linkage, and piston. By this addition of counterweight, an imaginary central axis of balance of the crankshaft remains aligned with the central axis of the shaft of the motor. The counter-weighing of the crankshaft is analogous to the well-known counterweight configuration of an oil well pump.
Dynamic balance is achieved by making that any combined inertial and gravitational moment of the rotating crankshaft perpendicular to the rotational axis of the crankshaft is everywhere equally opposite (not xe2x80x9ceverywhere equalxe2x80x9d, but xe2x80x9ceverywhere equally oppositexe2x80x9d). Notably, this inertial moment measured at the point of the attachment of the connecting linkage includes a nominal load as well as the connecting linkage and piston. The load on each piston of the shaker is thus intentionally kept relatively constant, making that sample containers that hold scant lightweight samplesxe2x80x94for example, a few microcapsulesxe2x80x94are relatively heavy while those sample containers that hold heavy samplesxe2x80x94for example a single large test tube containing nearly eight ounces of sample materialxe2x80x94are relatively light: oppositely to what might be expected.
Both the static and dynamic crankshaft balance are hard to visually identify and recognize, including in the drawings of this specification of the preferred embodiment of a reciprocating shaker in accordance with the present invention. It is thus necessary to think about this balance: exactly what it is, where it is located, and what it accomplishes.
Consider that the way that this balance is realized is not the only possibility. It might be imagined, as a hypothetical illustration of the principles of the present invention, that nearly perfect static and dynamic balance would be realized, save for the operation of gravity, if there was to be an identical (i) connecting linkage, (ii) piston and (iii) sample container load hypothetically affixed to one crankshaft at a point one hundred and eighty degrees opposite to the existing affixation point. However, since the hypothetical two linkages would then mechanically interfere with each other, a crankshaft would then have be extended in the manner of the crankshaft for a multi-cylinder opposed-cylinder internal combustion engine. One linkage and piston would point up; one linkage and piston (on the extension of a single crankshaft) would go down. This geometry was actually tried. It was found, however, to be impractical to oppositely replicate the (i) connecting linkage, (ii) piston and (iii) sample container, and to shake a sample upside down.
It might alternatively be hypothesized that the linkages and pistons of an extended single crankshaft should be laid out horizontally, as is analogous to the opposed pistons within the horizontally-opposed internal combustion engines of the famous Volkswagon(copyright) Beetle or Porshe(copyright) 911. (Volkswagon and Porshe are registered trademarks of the respective companies). Alas, it not practical to obviate the effects of gravity by extending each of two (i) connecting linkages and (ii) pistons oppositely in the horizontal, and shaking the samples sideways. Accordingly, the crankshaft and associated parts are preferably dynamically balanced to run as smoothly as possible at some predetermined rotational speed and load, and are more preferably balanced for maximum speed and maximum load.
In accordance with a third aspect of the present invention, and yet another application of the xe2x80x9cequal but oppositexe2x80x9d principle, the (i) connection of the connecting linkage and its piston to the crankshaft at one side of the shaker is one hundred and eighty degrees (180xc2x0) angularly opposite to (ii) the connection of other connecting linkage and its piston to the crankshaft at the other side of the shaker. This makes that when one piston, and its affixed sample container and sample, are going xe2x80x9cupxe2x80x9d, then the other piston and affixed sample container and sample are going xe2x80x9cdownxe2x80x9d, and vice versa. The action is analogous to the movement of pistons in an internal combustion engine, where the shaker of the present invention is analogous to a two-cylinder engine.
The xe2x80x9cupxe2x80x9d and xe2x80x9cdownxe2x80x9d inertial forces on the shaker apparatus induced by the oscillatory movement of (i) its parts and (ii) its load thus tend to cancel each other out. Additionally, because the resulting oscillatory torquing forces about the center of gravity of the shaker occur at a rates faster and forces lower than can bring the inertial mass of the shaker into synchronous vibration, the shaker will normally sit relatively quietly in place, perhaps shuddering slightly.
For such vibration as the shaker does incur, it is preferably mounted on a suspension which is normally comprised of springs and/or dampers/shock absorbers. For such (i) airborne and (ii) structureborne, or vibrational, noise as the shaker emits, it is preferably housed with a cabinet that particularly directed to dampening noise of both (i) airborne and (ii) structureborne types.
In total, the several separate, but complimentary, approaches of the present invention permit a powerful shaker to powerfully oscillate a large load at high frequency in but a small volume, with but tolerable vibration and noise. Like most mechanical devices the operation of which is readily understandable, the shaker of the present invention perhaps appears at first glance to be mundane. However, careful assessment of the shaker structure reveals it to incorporate many separate design decisions that produce, in aggregate, superior operational performance.
3. Advanced Jigs for Use With the Shaker of the Present Invention
The shaker of the present invention can be used simply to shake two simple platforms, to which platforms a laboratory experimentalist may attach anything desired. However, the shaker of the present invention is intended to be used with a limited number of versatile jigs. Each jig efficiently adapts from one to many of a large number of different laboratory containers to a standard shaker of the present invention.
The jigs are preferably constructed of lightweight and strong plastic. An inner portion of the jig is tailored to a particular sample container, and holds a number of these sample containers in a grid array. Typically the grid array holder may be loaded with any number of sample containers: one single sample container up to a large number of identical sample containers. The grid array holders are typically molded, and inexpensive. A large number of different grid array holders as are suitable to different types of sample containers all have the same external dimensions and form.
For example, at least two grid array holders are not even unique to the shaker of the present invention, and are derived from standard laboratory well plates. Namely, the laboratory standard well plate that holds ninety-six (96) two-milliliter (2 ml.) test cells, and also the standard well plate that holds four (4) fifteen-milliliter (15 ml.) test tubes, can both be used as grid array holders with the shaker of the present invention. Yet another grid array holder holds a single fifty milliliter (50 ml.) test tube.
It will be recognized that the two xe2x80x9csidesxe2x80x9d and two pistons of the shaker permit that two jigs, each with a grid array holder, will be simultaneously used. Accordingly, the nominal capacity of the shaker is 2xc3x9796=192 two-milliliter (2 ml.) test cells, or 2xc3x974=8 fifteen-milliliter (15 ml.) test tubes.
These grid array holders are loaded with sample containers and are then enclosed within an outer container.
The outer container preferably consists of a thin-wall box that is held, and adapted to the shaker, by (i) an internal external space frame (which may be, and often is, integral with the box) and (ii) a clamping mechanism, commonly an over-center latch. Although all components are most typically made of plastic, the grid array holder is typically the most inexpensive, the enclosing box somewhat more expensive while the external space frame and clamp is the most expensive component.
In use of the jig system of the present invention, an assortment of grid array holders will be procured for such laboratory sample containers of different sizes and configurations as are required to be shaken. A more limited number of enclosing boxes is also procured. Finally, a still more limited number of space frames are procured. Thus one space frame suffices to hold a number of different boxes where each different box typically holds a number of different grid array holders.
In this manner adaptation of additional sample containers to an existing shaking system requires that only limited additional jig components need be bought, and these additional components will most likely be of the more inexpensive varieties.
4. Programmability of the Shaker in Accordance With the Present Invention
The shaker of the present invention is programmable, and incorporates a microprocessor controller. A human operator specifies the speed and duration parameter of a shaking protocol, which protocol may extend over indefinitely many shaking and rest periods each of operator-defined duration. Once programmed, the shaker xe2x80x9cremembersxe2x80x9d the protocol, which may thereafter be invoked simply by pressing a button, most preferably a (i) programmable function (ii) push button switch. Alert and status indications in the form or visible (and/or audible) warnings and alerts are also made.